Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors

Abstract

The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by IGF-1R kinase inhibitors. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to IGF-1R kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by IGF-1R kinase inhibitors are also provided. pErk, HER3 and pHER are also demonstrated to be effective biomarkers for predicting sensitivity of tumor cells to IGF-1R kinase inhibitors.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 60 / 997,445, filed Oct. 3, 2007, which is herein incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0002]The present invention is directed to methods for diagnosing and treating cancer patients. In particular, the present invention is directed to methods for determining which patients will most benefit from treatment with an insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitor.[0003]Cancer is a generic name for a wide range of cellular malignancies characterized by unregulated growth, lack of differentiation, and the ability to invade local tissues and metastasize. These neoplastic malignancies affect, with various degrees of prevalence, every tissue and organ in the body.[0004]A multitude of therapeutic agents have been developed over the past few decades for the treatment of various types of cancer. The most commonly used types of antica...

AI Technical Summary

Benefits of technology

[0020]The present invention also provides a method of predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising: assessing the level of the biomarker pErk expressed by a tumor cell; and predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, wherein high levels of biomarker pErk expression by tumor cells correlates with low sensitivity to inhibition by IGF-1R kinase inhibitors.

[0021]The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising the steps of: diagnosing a patient's likely responsiveness to an IGF-1R kinase inhibitor by assessing the level of the biomarker pErk expressed by the tumor cells of the patient, wherein high levels of biomarker pErk expression by tumor cells correlates with low sensitivity to inhibition by IGF-1R kinase inhibitors, and administering to said patient a therapeutically effective amount of an IGF-1R kinase inhibitor if the patient is diagnosed to be potentially responsive to an IGF-1R kinase inhibitor.

[0022]The present invention also provides a method for treating tumors or tum...

Problems solved by technology

Unfortunately, none of the current chemotherapies possess such an ideal profile.

Additionally, for any given cancer type one frequently cannot predict which patient is likely to respond to a particular treatment, even with newer gene-targeted therapies, such as protein-tyrosine kinase inhibitors, ...

Images